Protein kinase C modulates transcriptional activation by the juvenile hormone receptor methoprene-tolerant

Abstract

Juvenile hormone (JH) controls many biological events in insects by triggering dramatic changes in gene expression in target cells. The Methoprene-tolerant (MET) protein, an intracellular JH receptor, acts as a transcriptional regulator and binds to the promoters of tissue- and stage-specific JH target genes when JH is present. Our recent study has demonstrated that the transcriptional activation by MET is modulated by a membrane- initiated JH signaling pathway, involving phospholipase C (PLC) and calcium/calmodulin-dependent protein kinase II (CaMKII). Here we report that protein kinase C (PKC) is another essential intermediate of this pathway. PKC was activated by JH and this action was PLC-dependent. Inhibition of the PKC activity substantially weakened the JH-induced gene expression in mosquito cells. RNAi experiments indicated that several PKC isoforms were involved in the JH action during the post- emergence development of adult female mosquitoes. JH treatment considerably increased the binding of MET to the promoters of JH response genes in cultured mosquito abdomens that were collected from newly emerged female adults. The JH-induced DNA binding of MET was hindered when the abdomens were treated with a PKC inhibitor and JH. Therefore, the results suggest that PKC modulates the transactivation activity of MET by enhancing the binding of MET to JH response elements in the JH target genes. This mechanism may allow for variable and stage- and tissue-specific genomic responses to JH.

Juvenile hormone-regulated alternative splicing of thetaimangene primes the ecdysteroid response in adult mosquitoes

“…This JH action requires a pathway containing RTK, PI3K, and Akt, which modulates the phosphorylation of pre-mRNA splicing factors, such as SRp63, SRp53, and SRp30. We have previously reported that the RTK-PLC pathway transduces JH signal through the cell membrane and converges on the Met/Tai receptor complex in the nuclei (21,22). The present study suggests that the RTK family is required for the JHinduced alternative splicing of AaTai, but PLC is not likely involved.…”

“…Anti-V5 tag antibody was from Thermo Fisher Scientific. Production of AaMet and AaTai (common region) antibodies has been described previously (22). To generate antibodies for AaEcR and AaUSP, the full-length coding regions of AaEcRb and AaUSPb were cloned into a pGEX-6p-1 plasmid (GE Healthcare).…”

“…More recently, we have reported that DNA binding of the Met-Tai complex to the JH response genes is modulated by phosphorylation of both Met and Tai in female A. aegypti mosquitoes (21). JH regulates the phosphorylation via a cell membrane-initiated signal pathway involving receptor tyrosine kinases (RTKs), phospholipase C (PLC), and protein kinase C (PKC) (21,22).…”

Krüppel homologue 1 acts as a repressor and an activator in the transcriptional response to juvenile hormone in adult mosquitoes

“…We have reported that JH activates the phospholipase C pathway in Ae. aegypti mosquitoes and subsequently activates calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) (Liu et al, 2015;Ojani et al, 2016). It is conceivable that Kr-h1 serves as the direct or indirect target of CaMKII or PKC, and that phosphorylation modification switches its function between an activator and a repressor.…”

Insulin/IGF signaling and TOR promote vitellogenesis via inducing juvenile hormone biosynthesis

“…In the genomic action, JH binds its intracellular receptor, methoprene-tolerant (Met), to induce the expression of a JH primary-response gene Krüppel-homolog 1 (Kr-h1) , which plays a central role in JH signaling (Jindra et al, 2013; Li et al, 2019). Meanwhile, JH signaling may be transduced via receptor tyrosine kinase (RTK) or G protein-coupled receptor (GPCR), putative plasma membrane receptors, to act in a nongenomic manner (Davey, 2000; Liu et al, 2015; Ojani et al, 2016; Bai and Palli, 2016). JH is one of the main gonadotrophic hormones that promote vitellogenesis in insects, including Vg production in the fat body via the genomic action as well as the development of follicular patency and thus Vg uptake by the maturing oocytes via the non-genomic action (Raikhel et al, 2005; Jing et al, 2018; Roy et al, 2018).…”